Functional characterization of two enhancers located downstream FOXP2

• Main Authors: Raúl Torres-Ruiz, Antonio Benítez-Burraco, Marta Martínez-Lage, Sandra Rodríguez-Perales, Paloma García-Bellido
• Format: Article
• Language: English
• Published: BMC 2019-05-01
• Series: BMC Medical Genetics
• Subjects: FOXP2; MDFIC; Speech and language impairment; Spanish; CRISPR-genome editing; Functional enhancers
• Online Access: http://link.springer.com/article/10.1186/s12881-019-0810-2

Abstract Background Mutations in the coding region of FOXP2 are known to cause speech and language impairment. However, it is not clear how dysregulation of the gene contributes to language deficit. Interestingly, microdeletions of the region downstream the gene have been associated with cognitive deficits. Methods Here, we investigate changes in FOXP2 expression in the SK-N-MC neuroblastoma human cell line after deletion by CRISPR-Cas9 of two enhancers located downstream of the gene. Results Deletion of any of these two functional enhancers downregulates FOXP2, but also upregulates the closest 3′ gene MDFIC. Because this effect is not statistically significant in a HEK 293 cell line, derived from the human kidney, both enhancers might confer a tissue specific regulation to both genes. We have also found that the deletion of any of these enhancers downregulates six well-known FOXP2 target genes in the SK-N-MC cell line. Conclusions We expect these findings contribute to a deeper understanding of how FOXP2 and MDFIC are regulated to pace neuronal development supporting cognition, speech and language.